Vascular mechanotransduction

Abstract

This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), including their sensing of mechanical stimuli and transduction of mechanical signals that result in the acute functional modulation and longer-term transcriptomic and epigenetic regulation of blood vessels. The mechanosensors discussed include ion channels, plasma membrane associated structures and receptors, and junction proteins. The mechanosignaling pathways presented include the cytoskeleton, integrins, extracellular matrix and intracellular signaling molecules. These are followed by discussions on mechanical regulation of transcriptome and epigenetics, relevance of mechanotransduction to health and disease, and interactions between ECs and VSMCs. Throughout this review, we offer suggestions for specific topics that require further understanding. In the closing section on Conclusions and Perspectives, we summarize what is known and point out the need to treat the vasculature as a system, including not only ECs and VSMCs, but also the extracellular matrix and other types of cells such as resident macrophages and pericytes, so that we can fully understand the physiology and pathophysiology of the blood vessel as a whole, thus enhancing the comprehension, diagnosis, treatment, and prevention of vascular diseases.

Endothelin Receptor Blockade Improves Cerebral Blood Flow-Mediated Dilation in a Mouse Model of Alzheimer’s Disease

“…This is supported by our finding that FMD was selectively reduced in the PCA of APPS-PS1 mice. Interestingly, there were no alterations in agonist (ACh)-dependent dilation or contractility, pointing to potential changes in the integrity of the endothelium rather than in the vasodilator machinery, which retains its capacity to respond to external stimuli such as ACh [30, 31]. The reduction in FMD in APP-PS1 mice was significant in PCA but not in peripheral arteries (MRA), suggesting that the endothelium was altered in cerebral but not in mesenteric arteries.…”

Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension

“…9 Although oxidative stress alone is not sufficient to induce remodeling, 10 Nox2 (NADPH oxidase 2)-derived radicals induced by AngII type 1 receptor (AT1R) activation are an important contributing mechanism to cerebrovascular remodeling. 11 However, other factors may also be important, including altered vascular smooth muscle cell mechanotransduction mechanisms, 12 mineralocorticoid signaling, 13 or calcium-activated chloride channel function. 14 Hypertension is also a common comorbidity with the reduced distensibility and compliance of vasculature known as arterial stiffening.…”

Lesion-specific suppression of YAP/TAZ by biomimetic nanodrug ameliorates atherosclerosis development

“…For the cellular uptake assays, MoNP-DiD or NP-DiD were incubated with untreated EC, TNFα-pretreated EC, TNFα-/anti-VCAM1-pretreated EC, Mo, and macrophages for 30 minutes and then replaced with fresh medium. For the SS experiment, MoNP-DiD were added to the circulating medium in a parallel plate flow system and allowed to interact with EC exposed to high or low SS (12 or 1 dyne/cm 2 ) for 2 hours [40]. The intracellular DiD signal was quantified using fluorescent imaging and flow cytometric analyses.…”